Lecture 3- quinolones, folic acid antagonists, urinary antiseptics

Question 1

fluoroquinolones MOA

Answer 1

target DNA gyrase, primarily in gram neg bac and topoisomerase IV in gram pos bac to inhibit DNA replication

• gyrase: intro negative supercoils into DNA to prevent excessive positive supercoiling
• topo: promote separation of cms DNA into daughter cells

Question 2

types of dna gyrase/topo inhibitor- fluoroquinolones (3)

Answer 2

1. ciprofloxacin
2. levofloxacin
3. moxi

Question 3

fluoroquinolones ROA

Answer 3

oral, IV, ophthalmic

Question 4

fluoroquinolones clearance

Answer 4

renal, dose adjust

Question 5

CIPROfloxacin indications

Answer 5

• most active agaisnt gram neg strains and enteric coliforms eg. penicillin, cephalosporins
• for travellers diarrhea
• in skin, bone and joint infections
• against P. aeruginosa
• should be AVOIDED in MRSA infections
• UTI but not first line (lower UTI mostly)

Question 6

levo and moxi coverage

Answer 6

• better covrage against gram POS org esp S. penumoniaea
• better cov against atypical pathogens eg. mycoplasm
• useful in resp infections

Question 7

fluoroquinolones adverse effects

Answer 7

• GI eg. diarrhea, nausea
• C. diff colitis
• headache dizziness
• phototox
• tendinitis
• prolong QT interval

Question 8

fluoroquinolones and tb

Answer 8

not as first line as they may mask sx of tb

Question 9

fluoroquinolones CI

Answer 9

myasthenia gravis- may exacerbate muscle weakness

Question 10

classes of folate syntehsis inhibitors (3)

Answer 10

1. sulfonamides
2. trimethoprim
3. cotrimoxazole

Question 11

sulfonamides MOA

Answer 11

competetive inhibitors of dihydropteroate synthase

bacteriostasis induced can be REVERsed by PABA

Question 12

sulfonamides distri

Answer 12

bound to serum albumin

distri well throughout bodily fluids and penetrate well into CSF

Question 13

sulfonamides elim

Answer 13

renal

Question 14

sulfonamide clinical uses

Answer 14

combined with trimethoprim

Question 15

sulfonamides adverse effects

Answer 15

• crystalluria (form acetylated product which is toxic and ppt at neutral or acidic pH)
• hypersen eg. rash
• hemolytic anemia
• kernicterus- CI in children (brain damage)

Question 16

trimethoprim MOA

Answer 16

potent inhibitor of bacterial dihydrofolate reductase

Question 17

trimethoprim resistance

Answer 17

in gram neg bacteria due to altered dihydrofolate reductase that has lower affinity for trimethoprim
efflux pumps

Question 18

trimethoprim absorption

Answer 18

rapid absorption with ORAL admin
widely distri into body
godoCSF penetration

Question 19

trimethoprim elim

Answer 19

renal, mostly unchanged

Question 20

trimethoprim adverse efefct

Answer 20

FOLIC ACID deficiency

anemai, leukopenia

Question 21

cotrimoxazole MOA

Answer 21

synergistic antimic activity with inhibitrion of two sequential steps

• sulfamethoxaxole inhibits incorporation of PABA into difolate acid
• trimeoprim prevents reduction of dihydrofolate to tetrathydrofoalte

Question 22

cotrimoxazole ROA

Answer 22

oral commonly

IV also can

Question 23

cotrimoxazole distribution

Answer 23

good CSF penetration, readiliy crosses BBB

Question 24

cotrimoxazole clearance

Answer 24

excreted in urine

Question 25

what does cotrimoxazole contain?

Answer 25

sulfamethoxolate and trimethoprim

Question 26

cotrimoxazole uses

Answer 26

UTRI resp tract infection MRS and comm acquried skin and soft tissue infection penumocystis pneumonia caused by PNEUMOCYSTIS JIROVECI

Question 27

cotrimoxazole adverse

Answer 27

skin rxn eg. rash photosen nausea vomitting megaloblastic anemia (folic acid ef)

Question 28

drug for urinary antiseptic (1)

Answer 28

nitrofurantoin

Question 29

nitrofurantoin use

Answer 29

lower UTI

Question 30

nitrofurantoin MOA

Answer 30

reduce drug to hgihly active intermediate that inhibits enzymes and disrupts synthesis of proteins, DNA, RNA

Question 31

nitrofurantoin spectrum

Answer 31

against e coli and enterococci | pos and neg

Question 32

nitrofurantoin ROA

Answer 32

oral

Question 33

nitrofurantoin absorption

Answer 33

rapidly from GIT

Question 34

nitrofurantoin distri

Answer 34

high urinary conc while limiting sytemic exposure | - high conc in urine fast--> lower systemic exposure of drug

Question 35

nitrofurantoin adverse

Answer 35

nausea, vomiting leukpenia, hemolytic anemia - hepatocellular damage - pulmn toxicity for eledrly

Question 36

nitrofurantoin CI

Answer 36

- imparied renal func - pregnant - infants <1 month

Question 37

classes of polymyxins (2)

Answer 37

1. polymyxin B | 2. colistin

Question 38

diff between polymyxin B and colistin

Answer 38

polymyxins B administered directly as active antibiotic vs colistin admin as inactive prodrug

Question 39

polymyxins MOA

Answer 39

bactericidal | disrupt structure of cell membrane phospholipid and increase cell permeability

Question 40

polymyxins spectrum of activity

Answer 40

NARROW spectrum, mainly gram NEG used for multidrug resistant gram neg bac not useful agaisnt atypical and gram POS

Question 41

polymyxins ROA

Answer 41

iv, inhalation

Question 42

polymyxins adverse

Answer 42

nephrotox | neurotox eg. confusion, hallucination

Question 43

fosfomycin spectrum

Answer 43

against wide range of gram POS and NEG

Question 44

fosfomycin MOA

Answer 44

interferes with cell wall synthesis

Question 45

fosfomycin MOA

Answer 45

interferes with cell wall synthesis

Question 46

advatnage / spectrum of fosfomycin

Answer 46

good against resistant bacteria

Question 47

fosfomycin uses

Answer 47

UTI

Question 48

fosfomycin ROA

Answer 48

rapid absorption with oral admin and is converted to fosfomycin poor systemic absorption

Question 49

adverse effects of fosfomycin

Answer 49

GI, headache, vaginitis

Question 50

anti protozoal agents

Answer 50

protozoal infectiosn in underdev countires | unicellular eukaryotes- have met processes closer to those of human

Question 51

how to treat amebiasis

Answer 51

chemotherapy 1. luminal- act on parasite in lumen 2. systemic- in intestinal wall and liver 3. mixed amebicides

Question 52

metronidazole MOA

Answer 52

serve as electron acceptor--> form cytotoxic free radicals that result in protein and DNA damage metro stronger against ANAEROBES

Question 53

metronidazole absorption

Answer 53

complteley and rapidly absorbed after ORAL adin

Question 54

metronidazole distri

Answer 54

distri well into body and in CSF

Question 55

metronidazole elim and met

Answer 55

heptaic met- accum in pt with severe hep disease | elim- in urine

Question 56

metronidazole adverse

Answer 56

GI, unpleasant metallic tast

Question 57

metronidazole pregnancy usage

Answer 57

cat B | avoid in first trimester

Question 58

who not to give cirpofloxacin to

Answer 58

<18 yo-- will hv joint problem | dont give for serious lower UTI, mostly for upper

Question 59

what to give for nail infections?

Answer 59

give orally- need to be absorbed systemically and accum at keratin give azoles